COVID-19, Intensive care, Major adverse cardiac effect, Mortality, Remdesivir
Citation Information :
Panda R, Singh P, Jain G, Saigal S, Karna ST, Anand A, Kodamanchili S, Brahmam D, Jha S, Shivhare A. Effect of Remdesivir Administration on Occurrence of Major Adverse Cardiac Events in Critically Ill COVID-19 Pneumonia: A Retrospective Observational Study. Indian J Crit Care Med 2022; 26 (9):993-999.
Background and objectives: Major adverse cardiac events (MACE) are frequent in coronavirus disease-2019 (COVID-19). Remdesivir is used worldwide for treatment in COVID-19. In this retrospective observational study, our primary objective was to assess the impact of remdesivir administration on the incidence of MACE and associated 28 day survival in critically ill patients admitted for moderate to severe COVID-19 pneumonia. Patients and methods: We analyzed the data of 437 patients admitted in intensive care unit (ICU) and divided them into two groups: R group (received remdesivir at ICU admission) and NR group (nonremdesivir) or based on the occurrence of MACE in ICU. We followed the data until discharge, death, or 28 days postadmission. Our primary objective was to investigate the log-odds of survival with remdesivir administration and a correlation/regression analysis of MACE with remdesivir administration in all included patients. Results: The incidence of MACE was 72 among 437 patients, with 17 (9.3%) patients in R group vs 55 (21.8%) in NR group (p <0.001). On performing correlation analysis between MACE and remdesivir administration, significant correlation coefficient of −0.168 (p = 0.004) was obtained. On regression analysis, the odds ratio for occurrence of MACE with remdesivir administration was 0.362 (regression coefficient: −1.014, p <0.001). It indicates a 64% decrease in the log-odds of MACE and a 16% increase in the log-odds of survival with remdesivir administration. All 72 patients with MACE had expired, suggesting a high mortality risk with cardiac complications. The odds ratio for mortality due to MACE with remdesivir administration was 0.216 (regression coefficient: −1.530, p −<0.001). It indicates a 79% decrease in the log-odds of death due to MACE with remdesivir administration. Conclusion: Our study showed significant reduction in MACE and mortality benefit in patients who received remdesivir in comparison to standard treatment.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497–506. DOI: 10.1016/S0140-6736(20)30183-5.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. Journal of the American Medical Association 2020;323(11):1061–1069. DOI: 10.1001/jama.2020.1585.
Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020;e200950. DOI: 10.1001/jamacardio.2020.0950.
Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;e201017. DOI: 10.1001/jamacardio.2020.1017.
Linschoten M, Peters S, van Smeden M, Jewbali LS, Schaap J, Siebelink HM, et al. Cardiac complications in patients hospitalised with COVID-19. Eur Heart J Acute Cardiovasc Care 2020;9(8):817–823. DOI: 10.1177/2048872620974605.
Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2 [published correction appears in Cardiovasc Res 2020;116(12):1994]. Cardiovasc Res 2020;116(6): 1097–1100. DOI: 10.1093/cvr/cvaa078.
US Food and Drug Administration. Coronavirus (COVID-19) update: FDA issues Emergency Use Authorization for potential COVID-19 treatment. 2020 [Accessed August 11, 2020]. Available from: https://www.fda.gov/news events/press announcements/coronavirus- covid-19-update-fdaissues-emergency-use-authorization-potentialcovid-19-treatment.
Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017;9(396):eaal3653. DOI: 10.1126/scitranslmed.aal3653.
Brown AJ, Won JJ, Graham RL, Dinnon KH 3rd, Sims AC, Feng JY, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res 2019;169:104541. DOI: 10.1016/j.antiviral.2019.104541.
Pizzorno A, Padey B, Julien T, Trouillet-Assant S, Traversier A, Errazuriz-Cerda E, et al. Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia. Cell Rep Med 2020;1(4):100059. DOI: 10.1016/j.xcrm.2020.100059.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome [published correction appears in Lancet Respir Med 2020]. Lancet Respir Med 2020;8(4):420–422. DOI: 10.1016/S2213-2600(20)30076-X.
Madjid M, Vela D, Khalili-Tabrizi H, Casscells SW, Litovsky S. Systemic infections cause exaggerated local inflammation in atherosclerotic coronary arteries: clues to the triggering effect of acute infections on acute coronary syndromes. Tex Heart Inst J 2007;34(1):11–18. PMID: 17420787.
Tessitore E, Carballo D, Poncet A, Perrin N, Follonier C, Assouline B, et al. Mortality and high risk of major adverse events in patients with COVID-19 and history of cardiovascular disease. Open Heart 2021;8(1):e001526. DOI: 10.1136/openhrt-2020-001526.
Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol 2020;75(18):2352–2371. DOI: 10.1016/j.jacc.2020.03.031.
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China [published correction appears in Intensive Care Med 2020]. Intensive Care Med 2020;46(5):846–848. DOI: 10.1007/s00134-020-05991-x.
Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol 2020;109(5):531–538. DOI: 10.1007/s00392-020- 01626-9.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507–513. DOI: 10.1016/S0140-6736(20)30211-7.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. Journal of the American Medical Association 2020;323(13):1239–1242. DOI: 10.1001/jama.2020.2648.
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of Covid-19–final report. N Engl J Med 2020;383(19):1813–1826. DOI: 10.1056/NEJMoa2007764.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med 2020;8(4):e26]. Lancet Respir Med 2020;8(5):475–481. DOI: 10.1016/S2213-2600(20)30079-5.
Touafchia A, Bagheri H, Carrié D, Durrieu G, Sommet A, Chouchana L, et al. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns [published online ahead of print, 2021]. Clin Microbiol Infect 2021;27(5):791.e5–791.e8. DOI: 10.1016/j.cmi.2021.02.013.
Spinner CD, Gottlieb RL, Criner GJ, Arribas López JR, Ca AM. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. Journal of the American Medical Association 2020;324(11):1048–1057. DOI: 10.1001/jama.2020.16349.
Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial [published correction appears in Lancet 2020;395(10238):1694]. Lancet 2020;395(10236):1569–1578. DOI: 10.1016/S0140-6736(20)31022-9.
WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al. Repurposed antiviral drugs for Covid-19–interim WHO solidarity trial results. N Engl J Med 2021;384(6):497–511. DOI: 10.1056/NEJMoa2023184.
de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A 2020;117(12):6771–6776. DOI: 10.1073/pnas.1922083117.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30(3):269–271. DOI: 10.1038/s41422-020-0282-0.
Pruijssers AJ, George AS, Schäfer A, Leist SR, Gralinksi LE, Dinnon KH 3rd, et al. Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Cell Rep 2020;32(3):107940. DOI: 10.1016/j.celrep.2020.107940.
Saeed S, Tadic M, Larsen TH, Grassi G, Mancia G. Coronavirus disease 2019 and cardiovascular complications: focused clinical review. J Hypertens 2021;39(7):1282–1292. DOI: 10.1097/HJH.0000000000002819.
Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int 2020;98(1):209–218. DOI: 10.1016/j.kint.2020.05.006.